NHP PILOT STUDY OF A NOVEL PROTEIN ADJUVANT FOR VACCINES AGAINST HUMAN PATHOGENS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 这项初步研究的目的是比较实验佐剂ROV-ASP-1与阴性对照(PBS，无佐剂)以及常用佐剂(CpG-C ISS-ODN)的免疫原性和安全性。2010年4月，6只雄性恒河猴被分配到这个项目中，并被分成三个试验组之一。用50ug纯化的rRBD(受体结合域)免疫原加对照或试验佐剂皮下免疫3次，第1组(n=1)接种PBS(无佐剂)，第2组(n=2)接种50ug的ROV-ASP-1，第3组(n=2)接种100ug的ROV-ASP-1，第4组(n=1)接种250ug的CpG-C ISS-ODN。在每次免疫前、免疫当天和免疫后7天采集血样，检测抗体和细胞因子反应。 第三次免疫后，抗体滴度显著升高。根据这些结果，最后两次免疫被推迟，直到抗体效价降低。每月采集血液监测抗体滴度和细胞因子反应。最近的结果表明，效价正在恢复到较低的水平，我们预计将在2011年3月对这些动物进行第四次也是最后一次免疫。在免疫前、免疫后7天、30天和60天采集血样，以测定抗体和细胞因子反应。还将在免疫后7天和60天收集淋巴活检，以监测免疫反应。所有动物将在免疫后第60天后被释放到TNPRC。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The purpose of this pilot study is to compare the immunogenicity and safety of the experimental adjuvant rOv-ASP-1 against a negative control (PBS, no adjuvant) as well as a commonly used adjuvant (CpG-C ISS-ODN). Six male rhesus macaques were assigned to this project in April 2010 and placed in one of three experimental groups. All animals were immunized subcutaneously three times with 50ug purified rRBD (receptor binding domain) immunogen plus a control or test adjuvant; Group 1 (n=1) received PBS (no adjuvant), Group 2 (n=2) received 50 ug rOv-ASP-1, Group 3 (n=2) received 100 ug rOv-ASP-1 and Group 4 (n=1) received 250 ug CpG-C ISS-ODN. Blood samples were collected prior to, the day of and seven days after each immunization to measure antibody and cytokine responses. After the third immunization, antibody titers were significantly elevated. Based on these results, the final two immunizations were postponed until the antibody titers diminished. Blood was collected monthly to monitor antibody titers and cytokine responses. Recent results indicate that titers are returning to lower levels and we anticipate immunizing the animals a fourth and last time in March 2011. Blood samples will be collected prior to, the day of and days 7, 30 and 60 post-immunization to measure antibody and cytokine responses. Lymph node biopsies will also be collected 7 and 60 days post-immunization to monitor immune responses. All animals will be released to the TNPRC after the Day 60 post-immunization.